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IL-1R3 Blockade Broadly Attenuates the Functions of Six Members of the IL-1 Family, Revealing Their Contribution to Models of Disease

IL-1R3 Blockade Broadly Attenuates the Functions of Six Members of the IL-1 Family, Revealing Their Contribution to Models of Disease

Jesper Falkesgaard Højen, Marie Louise Vindvad Kristensen, Amy S McKee, Megan Taylor Wade, Tania Azam, Lars P Lunding, Dennis M de Graaf, Benjamin J Swartzwelter, Michael Wegmann, Martin Tolstrup, Karsten Beckman, etc.

Nat Immunol. 2019 Sep;20(9):1138-1149.

PMID: 31427775

Abstract:

Interleukin (IL)-1R3 is the co-receptor in three signaling pathways that involve six cytokines of the IL-1 family (IL-1α, IL-1β, IL-33, IL-36α, IL-36β and IL-36γ). In many diseases, multiple cytokines contribute to disease pathogenesis. For example, in asthma, both IL-33 and IL-1 are of major importance, as are IL-36 and IL-1 in psoriasis. We developed a blocking monoclonal antibody (mAb) to human IL-1R3 (MAB-hR3) and demonstrate here that this antibody specifically inhibits signaling via IL-1, IL-33 and IL-36 in vitro. Also, in three distinct in vivo models of disease (crystal-induced peritonitis, allergic airway inflammation and psoriasis), we found that targeting IL-1R3 with a single mAb to mouse IL-1R3 (MAB-mR3) significantly attenuated heterogeneous cytokine-driven inflammation and disease severity. We conclude that in diseases driven by multiple cytokines, a single antagonistic agent such as a mAb to IL-1R3 is a therapeutic option with considerable translational benefit.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413397	IL-36β mouse			Price

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